Arginase Activity Inhibition With Thymoquinone Induces a Hybrid Type of Cell-Death in MDA-MB-231 Cell Line.

Arginase plays a crucial role in the urea cycle; it also has immunosuppressive and pro-tumor effects. The present study aimed to assess the effects of arginase inhibition by thymoquinone (2-Isopropyl-5-methyl-1,4-benzoquinone), an active compound of Nigella sativa, on cell death in the MDA-MB-231 triple-negative breast tumor cell line. Cell viability assays, Western blot analysis, and flow cytometry analysis were used to characterize oxidative stress and cell death.

Prognostic Significance of Combining Cytokeratin-19, E-Cadherin and Ki-67 Analysis in Triple-Negative Breast Cancer with Basal-Like and Non-Basal-Like Phenotype.

Triple-negative breast cancer (TNBC) is known to have the worst outcome compared to the other forms of breast cancer. Moreover, molecular markers identified basal-like breast cancer (BLBC) phenotypes to be also related to a worse prognosis. In this study, we evaluated by immunohistochemistry (IHC) the prognostic significance of combining Cytokeratin-19 (CK19), E-cadherin, and Ki-67 tissue expression in triple-negative breast cancer (TNBC) cases presenting a basal-like (BLBC) or a non-basal-like (n-BLBC) phenotype to improve the selection and the monitoring of BC patients with a more aggressive outcome.

Analysis of BRCA1 germline variants (exons 5, 11 and 20) in breast cancer families from Libya.

Breast cancer (BC) is a leading cause of cancer deaths in Libyan women. variants differ globally due to the diversity of genetic makeup and populations history. Their distribution, prevalence, and significance in Libyans remain largely unexplored.

Arginase is upregulated in healthy women infected by oncogenic HPV types.

Introduction: The implication of arginase enzyme in Human Papillomavirus (HPV) infections has not been clearly elucidated. The present study investigates whether HPV infection is correlated with changes in plasmatic arginase activity and cervical ARG1 and ARG2 mRNA expression among infected women negative for intraepithelial lesions (NIL).

Materiel And Methods: The present study included 300 women.

Indoleamine 2,3-dioxygenase gene expression and kynurenine to tryptophan ratio correlation with nasopharyngeal carcinoma progression and survival.

Introduction: Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive tryptophan-depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC.

Arginase is involved in cervical lesions progression and severity.

Background: Little is known about the relationship between arginase, an immunosuppressive enzyme, and cervical lesions. The present study is aimed at evaluating arginase activity in plasma and mRNA arginase isoforms expression in cervical cells of patients with abnormal cytology and identifying their relationship with Human papillomavirus (HPV) related parameters such as: HPV type, HPV circulating viral load and anti-HPV16 IgG.

Methods: This study included 77 women with cervical lesions and 95 matched controls.

Prevalence of antibodies against a cyclic peptide mimicking the FG loop of the human papillomavirus type 16 capsid among Tunisian women.

Background: In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies.

Government Ownership and Adaptation in Scale-Up: Experiences from Community-Based Family Planning Programme in the Democratic Republic of the Congo.

A systematic approach to scale-up was applied to expand an integrated package of family planning and primary healthcare services from the Democratic Republic of the Congo's South Kivu province to health zones in Lomami, Lualaba, and Kasai Central provinces. This approach was based on recommendations from the ExpandNet/WHO guide Beginning with the end in mind. The approach emphasized application of three recommendations: engaging government stakeholders, ensuring the relevance of the intervention, and tailoring the innovation to the setting.

Functional Polymorphisms and Gene Expression of TLR9 Gene as Protective Factors for Nasopharyngeal Carcinoma Severity and Progression.

Nasopharyngeal carcinoma (NPC) is a disease that is closely associated with EBV infection. Toll-like receptor 9 is an important factor mediating the interaction between EBV and the host immune response. Any genetic (single nucleotide polymorphisms, SNPs) or expression variation in TLR9 gene may modify the ability of the receptor to respond correctly to viral infection as in NPC.

Contribution of BRCA1 5382insC mutation in triple negative breast cancer in Tunisia.

Background: Triple negative breast cancer (TNBC) has been classified as a disease subgroup defined by the lack of expression of estrogen and progesterone receptors as well as the absence of the human epidermal growth factor receptor-2 (HER2) overexpression. Germline mutations in the BRCA1 gene have been associated with TNBC. Approximately 70% of breast cancers arising in BRCA1 mutation carriers and up to 23% of breast cancers in BRCA2 carriers display a triple negative phenotype.

Contribution of Nitric oxide synthase 3 genetic variants to nasopharyngeal carcinoma risk and progression in a Tunisian population.

Purpose: We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population.

Methods: 259 NPC patients and 169 healthy controls were enrolled into our case-control study. Blood samples were genotyped by the RFLP-PCR analysis.

Joint effect of smoking and NQO1 C609T polymorphism on undifferentiated nasopharyngeal carcinoma risk in a North African population.

Background: Nasopharyngeal carcinoma (NPC) has a higher incidence in North Africa than in most parts of the world. In addition to environmental factors such as Epstein-Barr virus infection and chemical carcinogen exposure, genetic susceptibility has been reported to play a key role in the development of NPC. NAD(P)H: quinone oxidoreductase 1 is a cytosolic enzyme that protects cells from oxidative damage.

Establishing a Multicenter Longitudinal Clinical Cohort Study in Ethiopia: Advanced Clinical Monitoring of Antiretroviral Treatment Project.

Background: The purpose of this paper is to describe the establishment of the Advanced Clinical Monitoring of ART Project in Ethiopia for monitoring and evaluation of the longitudinal effectiveness of the ART program and to show the opportunities it presents. This cohort was established in response to the 2005 call by WHO for establishing additional mechanisms for stronger monitoring of ART and the need for creating the platform to generate evidence to guide the care given for the ever increasing number of patients on ART in Ethiopia.

Method: A participatory and multi-stage process which started from a consensus building workshop and steered by a mother protocol as well as guiding documents which dictated the degree of engagement and expectations was followed.

E-cadherin genetic variants predict survival outcome in breast cancer patients.

Background: E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the cell-to-cell junctions' strength and leads to cell detachment and escape from the primary tumor site. In this prospective study, three functional single nucleotide polymorphisms (-347G/GA, rs5030625; -160C/A, rs16260; +54C/T, rs1801026), were found to modulate E-cadherin expression.

Prognostic value of indoleamine 2,3-dioxygenase activity and expression in nasopharyngeal carcinoma.

Indoleamine 2,3-dioxygenase (IDO) is an enzyme with an immunosuppressive effect whose function is diverted by tumor cells to counteract immune cell functions, inducing immune escape of tumor cells. The aim of this study was to investigate the clinical significance of IDO in nasopharyngeal carcinoma (NPC). Compared to controls, NPC patients' plasma IDO activity was significantly higher, especially among patients with metastatic cancer (p=0.

Molecular epidemiology and genotype distribution of Human Papillomavirus (HPV) among Arab women in the State of Qatar.

Background: Human Papilloma Virus (HPV) infection is the major cause of cervical cancer worldwide. With limited data available on HPV prevalence in the Arab countries, this study aimed to identify the prevalence and genotypic distribution of HPV in the State of Qatar.

Methods: 3008 cervical samples, exclusively of women with Arabic origin residing in Qatar were collected from the Women's Hospital and Primary Health Care Corporation in Doha, State of Qatar.

Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: susceptibility and prognostic implications in Tunisians.

Genome-wide Association Studies (GWAS) revealed novel genetic markers for breast cancer susceptibility. But little is known about the risk factors and molecular events associated with breast cancer in Arab Population. Therefore, we designed a broad study to investigate the susceptibility and prognostic implications of the GWAS breast cancer loci in the Tunisian population.

Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population.

Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon-intron boundaries using direct sequencing.

Epstein-Barr virus DNA quantification and follow-up in Tunisian nasopharyngeal carcinoma patients.

The prognostic value of the Epstein-Barr virus (EBV) DNA load in sera of nasopharyngeal carcinoma (NPC) patients measured before any treatment, after treatment and before relapse was assessed. The real-time polymerase chain reaction was used to detect the viral load levels among 74 NPC subjects. Patients were followed up for a period going from 1 to 6 years (median 4 years).

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients.

Purpose: Chronic hepatitis C progression is commonly attributed to the continuous activation of the immune response with an increased production of pro-inflammatory cytokines, leading to fibrosis and ultimately to cirrhosis. On the contrary, anti-inflammatory cytokines, mainly interleukin (IL)-10 have a modulatory effect on hepatic fibrogenesis. The association between individual polymorphisms within cytokine genes and hepatitis C outcome is often weak and non-informative.

Lack of association between human leukocyte antigen-E alleles and nasopharyngeal carcinoma in Tunisians.

Nasopharyngeal carcinoma (NPC), a cancer with a remarkable geographical and worldwide ethnic distribution, has been strongly associated with human leukocyte antigen (HLA) class I genes. The presence of additional HLA risk factors has been suggested by several reports. In the present study, we analyzed the implication of HLA-E gene polymorphisms in NPC susceptibility in Tunisians, a population characterized by an intermediate incidence of NPC with specific clinical features.

Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission.

Nevirapine resistance mutations arise commonly following single or extended-dose nevirapine (ED-NVP) prophylaxis to prevent mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), but decay within 6-12 months of single-dose exposure. Use of ED-NVP prophylaxis in infants is expected to rise, but data on decay of nevirapine resistance mutations in infants in whom ED-NVP failed remain limited. We assessed, in Ethiopian infants participating in the Six-Week Extended Nevirapine (SWEN) Trial, the prevalence and persistence of nevirapine resistance mutations at 6 and 12 months following single-dose or up to 6 weeks of ED-NVP, and correlated their presence with the timing of infection and the type of resistance mutations.

Association of HLA-G polymorphisms with nasopharyngeal carcinoma risk and clinical outcome.

The expression of human leukocyte antigen-G (HLA-G) in tumor cells may facilitate the escape of the tumor from immunosurveillance; thus the aim of this study was to evaluate the influence of HLA-G polymorphisms occurrence on nasopharyngeal carcinoma (NPC) susceptibility, severity, and survival. Using the restriction fragment length polymorphism-polymerase chain reaction and the amplification refractory mutation system-polymerase chain reaction method, 186 Tunisian patients and 189 healthy controls were genotyped for nonsynonymous polymorphisms in HLA-G codon 31Thr/Ser, codon 110Leu/Ile and codon 130Leu/framshift. When allele, genotype and haplotype frequencies between patients and controls were compared for each single nucleotide polymorphisms (SNP), no statistical significant differences were observed.

Combined analysis of interferon-gamma and interleukin-10 gene polymorphisms and chronic hepatitis C severity.

Today there is increasing evidence concerning the contribution of pro-/anti-inflammatory cytokine balance and genetic factors in hepatitis C pathogenesis and interindividual heterogeneity of disease outcome. In the current study, we investigated the influence of functionally described single nucleotide polymorphisms (SNPs) present in interferon-gamma (IFNgamma) and interleukin-10 (IL-10) genes, on chronic hepatitis C severity. IFNgamma (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 100 hepatitis C patients with different disease severities (chronic hepatitis, n = 42, liver cirrhosis [LC], and hepatocellular carcinoma in liver cirrhosis [HCC], n = 58) and 103 healthy controls using allele-specific polymerase chain reaction.